Epigenetic repression of THBD transcription by BRG1 contributes to deep vein thrombosis.

BACKGROUND: Deep vein thrombosis (DVT) with its major complication, pulmonary embolism, is a global health problem. Endothelial dysfunction is involved in the pathogenesis of DVT. We have previously demonstrated that endothelial specific deletion of Brahma-related gene 1 (BRG1) ameliorates atherosclerosis and aneurysm in animal models. Whether endothelial BRG1 contributes to DVT development remains undetermined. METHODS: DVT was induced in mice by ligation of inferior vena cava. Deletion of BRG1 in endothelial cells was achieved by crossing the Cdh5-ERT-Cre mice with the Brg1loxp/loxp mice. RESULTS: Here we report that compared to the wild type mice, BRG1 conditional knockout (CKO) mice displayed substantially decreased DVT susceptibility characterized by decreased weight and size of thrombus and reduced immune infiltration. In endothelial cells, thrombomodulin (THBD) expression was significantly decreased by TNF-α stimulation, while BRG1 knockdown or inhibition recovered THBD expression. Further analysis revealed that BRG1 deficiency decreased the CpG methylation levels of the THBD promoter induced by TNF-α. Mechanistically, BRG1 directly upregulated DNMT1 expression after TNF-α treatment in endothelial cells. More importantly, administration of a small-molecule BRG1 inhibitor PFI-3 displayed potent preventive and therapeutic potentials in the DVT model. CONCLUSIONS: Our findings implicate BRG1 as an important regulator of DVT pathogenesis likely through epigenetic regulation of THBD expression in endothelial cells and provide translational proof-of-concept for targeting BRG1 in DVT intervention.

[Building virtual simulation teaching platform based on electronic standardized patient].

Informatization is an effective way to promote the reform and innovation of higher education and improve its quality. Virtual simulation teaching is indispensable in the educational informatization. Here, we describe the development and current situation of virtual simulation teaching, and introduce electronic standardized patient (ESP) based-virtual human body system powered by the real-time human physiological parameters. We also discuss how to build an ESP-based community in the teaching of human physiology, preclinical integrated case learning and other teaching projects. These ESP-based virtual simulation projects display the advantages of interdisciplinary fusion and the combination of basic and clinical knowledge, and open up the third type of functional experiments. Therefore, ESP-based virtual simulation teaching platform presumably becomes a considerable option for the first-class course construction in physiology.